1. Date of download: 6/6/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Lessons Learned From Fatal Progressive Multifocal Leukoencephalopathy in a Patient With Multiple Sclerosis Treated With Natalizumab JAMA Neurol. 2013;70(3):398-402. doi:10.1001/jamaneurol.2013.1960 Figure 1. Magnetic resonance imaging scans obtained 1 year prior to symptom onset (scan 1), 1 month prior to hospital admission (scan 2), and during hospital stay (scan 3). All magnetic resonance images were at 1.5 T. From left to right: sagittal fluid-attenuated inversion recovery (FLAIR); axial FLAIR at the level of the periatrial white matter of the lateral ventricles; corresponding postgadolinium T1; axial FLAIR at the level of the upper lateral ventricles and periventricular white matter; and corresponding T1 axial postgadolinium images. A, Scan 1, September 2010. The FLAIR images demonstrate abnormal foci of increased T2 signal radiating away from the ventricles in a perpendicular fashion with involvement of the corpus callosum (arrow). Corresponding T1 postgadolinium images show no evidence of gadolinium enhancement to suggest active inflammation. B, Scan 2, October 2011, after onset of visual symptoms. The FLAIR images demonstrate new increased T2 signal changes extending into the right occipital and right parietal lobes (arrows). Postcontrast images do not demonstrate corresponding contrast enhancement. C, Scan 3, November 2011, 1 month after onset of progressive multifocal leukoencephalopathy–related symptoms. The FLAIR images demonstrate progression of white matter increased T2 signal changes, most notable in the right occipital, left occipital, and left frontal lobes with involvement of both white and gray matter (arrows). Postcontrast images demonstrate the vasculature without enhancement in the corresponding white matter. Figure Legend:

2. Date of download: 6/6/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Lessons Learned From Fatal Progressive Multifocal Leukoencephalopathy in a Patient With Multiple Sclerosis Treated With Natalizumab JAMA Neurol. 2013;70(3):398-402. doi:10.1001/jamaneurol.2013.1960 Figure 2. Immunohistochemical characterization of progressive multifocal leukoencephalopathy–induced white matter and cortical demyelination. A, Example of a tissue section labeled with proteolipid protein (PLP) showed a subcortical white matter lesion (WML) (1) that expands into the lower layers of the adjacent cortex (CL) (2). There are additional patchy areas of cortical demyelination. Myelinated white matter and cortex are labeled as normal-appearing white matter (NAWM) (3) and normal-appearing gray matter (NAGM), respectively. B and C, Immunostaining with CD68, a marker for microglia and macrophages, shows swollen, myelin-laden macrophages in demyelinated white matter (B, arrows) and adjacent demyelinated cortex (C, arrows). D, Normal adjacent white matter and normal-appearing cortex contained ramified microglia (arrow). E and F, Immunolabeling with the astroglial marker glial fibrillary acidic protein (GFAP) demonstrates ballooned and highly reactive astrocytes within white matter and cortical lesions (arrows). G, In contrast, in NAWM, astrocytes were small and had thin, elongated processes (arrows). H, The JC virus capsid protein VP-1 was expressed in demyelinated white matter predominantly in the cytoplasm of reactive astrocytes (arrows). I, In contrast, in cortical lesions, VP-1 was present predominately within neuronal cytoplasm and oligodendrocytes (arrows). J, In normal adjacent white matter, VP-1 was expressed in occasional oligodendrocytes (arrow) (parts B-J counterstained with hematoxylin). Figure Legend: